title: Ubiquilin 2 is not associated with tau pathology.
abstract: Accumulation of aberrant proteins in inclusion bodies is a hallmark of many neurodegenerative diseases. Impairment of proteolytic systems is a common event in these protein misfolding diseases. Recently, mutations in the UBQLN 2 gene encoding ubiquilin 2 have been identified in X-linked amyotrophic lateral sclerosis (ALS). Furthermore, ubiquilin 2 is associated with inclusions in familial and sporadic ALS/dementia, synucleinopathies and polyglutamine diseases. Ubiquilin 2 exerts a regulatory role in proteostasis and thus it has been suggested that ubiquilin 2 pathology may be a common event in neurodegenerative diseases. Tauopathies, a heterogenous group of neurodegenerative diseases accompanied with dementia, are characterized by inclusions of the microtubule-binding protein tau. In the present study, we investigate whether ubiquilin 2 is connected with tau pathology in Alzheimer's disease (AD), supranuclear palsy (PSP) and Pick's disease (PiD) and familial cases with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We show that ubiquilin 2 positive inclusions are absent in these tauopathies. Furthermore, we find decreased ubiquilin 2 protein levels in AD patients, but our results do not indicate a correlation with tau pathology. Our data show no evidence for involvement of ubiquilin 2 and indicate that other mechanisms underly the proteostatic disturbances in tauopathies.
authors.affiliation: Department of Genome Analysis, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Nölle
authors.forename: Elise S
authors.initials: ES
authors.lastname: van Haastert
authors.forename: Rob
authors.initials: R
authors.lastname: Zwart
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.forename: Wiep
authors.initials: W
authors.lastname: Scheper
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D014452:Ubiquitins / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D018797:Cell Cycle Proteins; C405662:UBQLN2 protein, human; D014452:Ubiquitins; D016875:tau Proteins